Both epidemiological and experimental studies indicate that dietary fiber may play an important role in the prevention of colorectal cancer. Current evidence suggests that fiber may inhibit colon carcinogenesis by diluting out any carcinogens and promoters present in the intestinal contents, reducing their mucosal contact time adsorbing them. The relative importance of these effects has still not been well defined. Recent work from this laboratory has shown that dietary fiber influences intestinal mucosal growth and cell proliferation. Dietary fibers may also produce acidification of colonic contents which in turn influences colonic metabolism and function. The aims of this proposal are to examine the relative importance of these changes in cell proliferation and fecal pH on the development of colonic cancer. Colonic tumors will be induced in male Sprague-Dawley rats using the carcinogen 1,2-dimethylhydrazine (DMH). The rats will be divided up prior to receiving DMH so that one group is fed a fiber-free diet and the experimental groups a similar diet with the addition of either 20% wheat bran, 20% oat bran, 10% pectin or a 10% guar supplement. The effect of these different diets on tumor induction rates and intestinal epithelial cell cytokinetics will be measured and correlated with tumor development. These fibers were chosen because wheat bran stimulates epithelial cell growth, increases fecal bulk, and increases the rate of intestinal transit, while oat bran affects fecal bulk and intestinal transit time but not mucosal cell growth, whereas pectin and guar both stimulate mucosal cell growth without altering the bulk or transit rate of intestinal contents. In the second half of the proposal the effect of fecal pH on rat tumor induction with DMH will be investigated by feeding a non-absorbable carbohydrate, lactulose or sorbitol which produces acidification of large bowel contents. The effect of these treatments on the rates of intestinal tumor induction will be measured and correlated with any alterations in cell cytokinetics and fecal bile acid profiles that occur. The results of these studies will extend our understanding of how dietary fiber inhibits the development of colorectal cancer. This information may ultimately be applied to the design of human protocols to be used in dietary intervention studies for cancer prevention.